细胞致死性膨胀毒素损伤宿主防御机制研究进展

Cytolethal distending toxin injures host defense mechanism

细胞致死性膨胀毒素(cytolethal distending toxin,CDT)属于AB_(2)毒素,由多种革兰氏阴性菌产生。CDT是第一种被描述的细菌基因毒素,编码3种多肽:CDTA、CDTB和CDTC。CdtB是活性部分,有损伤多种细胞类型的能力。CDT具有一种新的分子作用模式,会干扰真核细胞周期的进展,从而导致G2/M停滞和细胞凋亡,该作用机制针对细胞,而且现阶段对于CDT的研究更多也是细胞层面,但是CDT作为毒力因子最终作用是损伤宿主造成疾病。但目前对CDT与宿主相互作用的分子机制了解尚不清晰。本文对细胞致死性膨胀毒素作为毒力因子从损伤上皮屏障、适应性免疫以及促进炎症反应三方面来综合阐述其对宿主防御机制途径的损伤,以期了解其致病机制以及为其临床治疗提供理论依据和新思路。

Cytolethal distending toxin(CDT)is an AB2 toxin produced by a variety of Gram-negative bacteria.It was the first bacterial genotoxin described,encoding three polypeptides:CDTA,CDTB,and CDTC.CdtB is the active moiety that has the ability to damage multiple cell types.CDT has a new molecular mode of action,which can interfere with the progress of eukaryotic cell cycle,resulting in G2/M arrest and apoptosis.Such mechanism of action targets cells,and the available studies of CDT concentrate on the cellular level.However,CDT,as a virulence factor,ultimately causes pathogenic damage to the host,and the molecular mechanism of CDT-host interaction remains unclear.This paper comprehensively expounded the damage of CDT as a virulence factor to the host defense mechanism from three aspects,including damage to the epithelial barrier,acquired immunity,and promotion of inflammatory response,aiming to reveal the pathogenic mechanism of CDT and provide a theoretical basis and new ideas for clinical treatment.